Identification of Alveolar Rhabdomyosarcoma "Achilles' Heel"

Alveolar rhabdomyosarcoma is a malignant tumor that originates in the muscle. It mostly affects young children. Its treatment involves surgery, radiation and chemotherapy. These therapies have many side effects and are significantly toxic. Unfortunately, children with distant metastases and patients with recurrent disease have a very poor prognosis.

Tumor cells are different from normal cells: we know that they activate distinct genes to grow. We believe that if we can identify the genes that are essential for tumor growth and develop therapies that specifically target them, we will be able to abolish the survival advantage that tumor cells have and improve chances of survival in patients affected by this disease.

We can now silence genes one at a time using a technique called "RNA interference". By doing so, we can detect which one is critical for the cells to continue growing. We have done preliminary work in this area that led us to the identification of a gene that encodes for a protein that significantly affects rhabdomyosarcoma growth. We propose to design a rational screen to identify candidates for targeted alveolar rhabdomyosarcoma therapy.